Process for the preparation of halogenated benzoic acid derivatives

Abstract

The present invention comprises a process for the preparation of 3-chloro-2-fluoro-5-trifluoromethyl benzoic acid of the formula or of a salt thereof 3-Chloro-2-fluoro-5-trifluoromethyl benzoic acid or salts thereof are versatile intermediates for the preparation of active pharmaceutical or agrochemical agents.

The invention claimed is: 
     
       1. A process for the preparation of 3-chloro-2-fluoro-5-trifluoromethyl benzoic acid of the formula 
       
         
           
           
               
               
           
         
         or of a salt thereof, comprising the steps of 
         a) transforming the 3-chloro-4-fluoro-benzo trifluoride of formula II, 
       
       
         
           
           
               
               
           
         
         into the 3-chloro-2-fluoro-5-trifluoromethyl benzaldehyde of formula III, 
       
       
         
           
           
               
               
           
         
         and 
         b) oxidizing the 3-chloro-2-fluoro-5-trifluoromethyl benzaldehyde with an oxidant to form the 3-chloro-2-fluoro-5-trifluoromethyl benzoic acid of formula I or of a salt thereof. 
       
     
     
       2. The process of  claim 1 , wherein the transformation into the 3-chloro-2-fluoro-5-trifluoromethyl benzaldehyde of the formula III is performed by deprotonating the 3-chloro-4-fluoro-benzo trifluoride with a metalorganic base followed by adding an electrophile in an organic solvent at a reaction temperature of −100° C. to 25° C. 
     
     
       3. The process of  claim 2 , wherein a protic acid as quenching agent is added subsequent to the deprotonation and subsequent to the addition of the electrophile. 
     
     
       4. The process of  claim 2 , wherein the metalorganic base is selected from n-butyl lithium, and lithium diisopropylamide. 
     
     
       5. The process of  claim 2 , wherein the electrophile is selected from an N,N-dialkylformamide, an N,N-diarylformamide or an N-alkoxy-N-alkyl formamide. 
     
     
       6. The process of  claim 1 , wherein the oxidant is selected from alkali- or alkali earth hypochlorites, -hypobromites, -chlorites, -chlorates, -persulfates or -permanaganates. 
     
     
       7. The process of  claim 6 , wherein the reaction is performed in the presence of an alkali hydroxide base and an alkali bromide in an aqueous solvent at a reaction temperature of 10° C. to 100° C. 
     
     
       8. The process of  claim 1 , wherein the 3-chloro-2-fluoro-5-trifluoromethyl benzaldehyde of the formula III is not isolated prior to the oxidation in step b 2 ).